A recent study showed that the long isoform of interleukin-1 receptor-associated kinase 4 (IRAK4) was the dominant alternatively spliced isoform and highly expressed in CD34+ HSPCs from MDS and AML patients harboring U2AF1 mutations, and inhibition of the long isoform of IRAK4 abrogated disease growth in AML xenografts. Here, IRAK4 is linked to myelodysplastic syndrome.